CN114652706B - Application of dendrobinol and composition thereof in preparation of medicines for treating allergic skin diseases - Google Patents

Application of dendrobinol and composition thereof in preparation of medicines for treating allergic skin diseases Download PDF

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Publication number
CN114652706B
CN114652706B CN202210294045.9A CN202210294045A CN114652706B CN 114652706 B CN114652706 B CN 114652706B CN 202210294045 A CN202210294045 A CN 202210294045A CN 114652706 B CN114652706 B CN 114652706B
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dendrobinol
allergic skin
skin diseases
allergic
application
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CN114652706A (en
Inventor
王伟
张扬
陈爽爽
汪义媛
李育鹏
胡润凡
陈杜艳
李锦骁
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Hefei Normal University
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Hefei Normal University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/075Ethers or acetals
    • A61K31/085Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention discloses application of dendrobinol and a composition thereof in preparing medicines for treating allergic skin diseases, and belongs to the technical field of novel medical application of traditional Chinese medicine active ingredient dendrobinol. In particular to the application of dendrobinol in preparing medicaments for treating allergic skin diseases, wherein the allergic skin diseases comprise urticaria, eczema, contact dermatitis, atopic dermatitis, allergic purpura and drug eruption. The animal test results show that: the dendrobine phenol can inhibit the inflammatory reaction, ear swelling and scratching times of a guinea pig allergic skin disease model induced by 2, 4-dinitrochlorobenzene, and reduce eosinophil infiltration and mast cell infiltration of an affected part, so that the dendrobine phenol has the effects of resisting allergic reaction, detumescence and relieving itching, and has a good treatment effect on allergic skin diseases.

Description

Application of dendrobinol and composition thereof in preparation of medicines for treating allergic skin diseases
Technical Field
The invention belongs to the technical field of novel medical application of active component dendrobinol of traditional Chinese medicinal materials, and particularly relates to application of dendrobinol in preparation of medicines for treating allergic skin diseases, wherein the allergic skin diseases comprise urticaria, eczema, contact dermatitis, atopic dermatitis, allergic purpura and drug eruption.
Background
Allergic skin diseases are one of the most common allergic diseases, and are mainly characterized by various skin symptoms caused by type I allergy, and are specifically characterized by various dermatitis, eczema, urticaria and the like. Various allergens can cause the skin to have the effects of dilating capillary blood vessels, enhancing permeability, infiltrating inflammatory cells, releasing various allergic mediums and stimulating peripheral nerve cells, thereby showing skin rash, fester and the like. Allergic skin diseases are easy to repeatedly occur, and the affected part often shows severe itching, which seriously affects the life, study and working quality of patients.
At present, local external hormone and oral antihistamine medicines are mainly adopted for clinical treatment of allergic skin diseases at home and abroad, but adverse reactions such as damaged skin barrier function and central nervous system inhibition and the like induced by the medicines further limit the clinical application of the medicines. Therefore, it is important to find and develop safe and effective anti-allergic skin diseases drugs.
Dendrobium phenol (Gigantol), a dibenzyl phenolic substance, is extracted from root of herba Dendrobii, and is one of the medicinal effective components of herba Dendrobii. The related researches find that the dendrobium has various biological activities, including enhancing the immunity of organisms, helping digestion of stomach, resisting cataract, regulating blood sugar, resisting tumor and the like.
To date, no report has been made on the use of dendrobinol as a drug for treating allergic skin diseases.
Disclosure of Invention
Technical problems: the invention aims to solve the technical problem of providing application of dendrobinol in preparing medicines for treating allergic skin diseases.
The invention also solves the technical problem of providing application of a composition containing dendrobe in preparing medicines for treating allergic skin diseases.
The technical scheme is as follows: in order to solve the technical problems, the invention provides the following technical scheme:
application of dendrobinol in preparing medicines for treating allergic dermatoses is provided.
The structural formula of the dendrobe phenol is shown as a formula (I):
use of a composition comprising dendrobe in the manufacture of a medicament for the treatment of allergic skin conditions.
Wherein the allergic skin disease comprises: eczema, urticaria, contact dermatitis, atopic dermatitis, allergic purpura, and allergic drug eruptions.
Further, the dendrobinol is matched with auxiliary materials of corresponding dosage forms to prepare oral liquid, injection, tablet, pill, dispersing agent, capsule, soft capsule, dripping pill, granule, solution, suspending agent, emulsion or microcapsule.
The auxiliary materials comprise: excipients and diluents; the excipient comprises binding agent, filler, disintegrating agent, lubricant, antiseptic, antioxidant, correctant, aromatic, cosolvent, emulsifier, solubilizer, osmotic pressure regulator, colorant, etc., and the diluent comprises physiological saline, starch, dextrin, sucrose, lactose, etc.
Preferably, the composition comprises: dendrobe phenol, stearic acid, potassium carbonate, glycerol monostearate, triethanolamine and clove oil.
Further preferably, the mass ratio of the dendrobe to the stearic acid to the potassium carbonate to the glycerol to the glyceryl monostearate to the triethanolamine to the clove oil is 0.25g:0.55g:0.045g:0.5g:0.125g:0.015mL:0.035mL.
The technical method provided by the invention can be a single component of dendrobe, or can be a medicament which comprises dendrobe as a basic active component and pharmaceutically acceptable auxiliary agents.
The beneficial effects are that:
the invention provides a preparation method of dendrobinol (health care product or medicine) with therapeutic effect on allergic skin diseases, which is used for treating allergic skin diseases. The invention has the following obvious progress and advantages:
1. the components are definite (dendrobinol); 2. definite target (allergic skin disease); 3. has definite regulating effect (obvious improving and treating effect).
Proved by a classical allergic skin disease animal model unfolding pharmacological experiment, the research result shows that the dendrobinol can obviously reduce the skin damage score, ear thickness, epithelial cell proliferation and scratching times of the model animal, reduce the eosinophil and mast cell number of an affected part and inhibit inflammation and allergy. The experimental result proves that the dendrobinol has definite therapeutic effect on allergic skin diseases.
Drawings
Figure 1 right ear skin lesions of guinea pigs of each group after 4 days of treatment.
Figure 2 control, model, paeonol, dendrobe skin lesion score, ear thickness, hematoxylin-eosin (HE) staining results. * P<0.05 compared to the model set; # P<0.05 compared to the paeonol group.
FIG. 3 results of scratching times within 20min for control, model, paeonol, dendrobe. * P<0.05 was compared to the model set.
Figure 4 results of control, model, paeonol, dendrobe Toluidine Blue (TB), congo red staining (CR). * P<0.05 was compared to the model set.
Detailed Description
The invention will be better understood from the following examples. However, it will be readily appreciated by those skilled in the art that the description of the embodiments is provided for illustration only and should not limit the invention as described in detail in the claims.
Example 1: effect of dendrobinol on guinea pig model of allergic skin disease.
1. Experimental animals: guinea pigs weighing 220-250 g, supplied by the nux-vow farm in the region of the pu's mouth, animal production license number: SCXK 2019-0005, male and female halves.
2. Preparing the medicine: dendrobe phenol (0.25 g), stearic acid (0.55 g), potassium carbonate (0.045 g), glycerol (0.5 g), glyceryl monostearate (0.125 g), triethanolamine (0.015 mL) and clove oil (0.035 mL) are prepared into dendrobe emulsifiable paste. The emulsification temperature was 70℃and the dose was 2.5 g/kg/dose.
The experimental method comprises the following steps:
(1) And (3) molding: after the animals had been acclimatized for 1 week, the allergic skin disease model was replicated by 1-chloro-2, 4-Dinitrobenzene (DNCB) induction, the guinea pigs were dehaired on both sides of the back 1 day prior to the experiment, approximately 2cm x 2cm in area, and 25. Mu.L of 5% DNCB (formulated on 4:1 acetone olive oil as matrix) solution was applied to the shaved sites on the day of the experiment Tu Zhimin. After two weeks, 100. Mu.L of DNCB solution at 0.1% (1 mg/L) was applied as a challenge to the inner side of the right ear of each guinea pig, 1 time per week, four times continuously. If local swelling occurs at the medicine applying part within 48 hours after the last excitation, skin pathology can be seen to be hyper-proliferation, hyperkeratosis, erythema, scales, edema, scratch and the like after 72 hours, and the modeling is successful.
Grouping and processing: guinea pigs successfully molded were randomly divided into 3 groups (6-8 per group): model group, dendrobii phenol group, paeonol group (positive drug control group, commercial paeonol ointment). Normal guinea pigs without molding were also taken as control groups (6-8). The dendrobium phenol group and the paeonol group are applied to the skin for administration 2 times daily, and the administration time interval of 2 times is 8 hours, and the dendrobium phenol group and the paeonol group are continuously used for 10 days. The control and model groups were daily coated with an ointment base without dendrobine. The time and frequency of administration were the same as in the drug-treated group.
(2) Skin lesion symptom score: the skin lesions of the guinea pigs of each group were observed visually, and mainly the presence or absence of erythema, edema, epidermolysis, lichenification and the like were observed. Scoring was performed using the simplified version EASI method. Erythema: no 0 score, slightly 1 score, 2 scores of moderate erythema with light and moderate crust, and 3 scores of severe erythema with severe crust; edema: no score of 0, mild score of 1, moderate score of 2 and severe score of 3; degree of dry cracking: no score of 0, mild score of 1, moderate score of 2 and severe score of 3; mossization: no score of 0, mild score of 1, moderate score of 2 and severe score of 3.
(3) Ear thickness: during the drug treatment period, the thickness of the skin of each group of guinea pigs is measured by an electronic vernier caliper every day, and the thickening conditions of the skin of each group are compared.
(4) Number of scratches: the last day of treatment, the number of scratches (rubbing the nose, ears and back skin with the hind paws) was observed and recorded in each group of guinea pigs for 20min, and the effect of the drug on skin itching was analyzed.
(5) Histopathological observation: the final day of treatment, guinea pigs were anesthetized intraperitoneally with anesthetic, 8mm skin biopsies were taken, fixed in 4% paraformaldehyde solution, paraffin sections were prepared, HE, TB, CR staining was performed, and each group of guinea pigs was observed for histopathological changes and inflammatory cell infiltration under an optical microscope (100×). The number of cells was counted using Image J software.
(6) Statistical analysis: statistical analysis was performed using GraphPad Prism 8.0 software, experimental data expressed as mean ± standard error (x±s), and group differences were analyzed using One-way Anova in combination with Post Hoc (Dunnett method).
4. Experimental results:
as shown in fig. 1: compared with the control group, the skin of the right ear of the guinea pig in the model group is obviously thickened, desquamation, fresh and changed fur, dryness, and erythema with different degrees at the gap part of the crust, scattered in a little pimple and exudation; on the 4 th day of treatment, compared with the model group, the dendrobium phenol group has the advantages of fading red spot, reducing edema, fading, scab skin falling off and better skin damage improvement degree than the paeonol ointment as a positive control medicine.
As shown in fig. 2: the model group guinea pigs had significantly increased skin lesion score, ear thickness and epithelial cell proliferation compared to the control group; compared with the model group, the score of the skin damage of the right ear, the ear thickness and the epithelial cell proliferation of the dendrobe phenol group are obviously reduced, and the score of the skin damage of the dendrobe phenol group is obviously lower than that of the paeonol group on the 4 th day of treatment, so that the dendrobe phenol can obviously improve the symptoms related to allergic skin diseases, and the onset time is faster than that of the paeonol ointment which is a positive control medicine.
As shown in fig. 3: the number of scratches was significantly increased in the model group guinea pigs for 20min compared to the control group. Compared with the model group, the scratching times of the dendrobe phenol group are obviously reduced, which suggests that the dendrobe phenol has obvious inhibition effect on skin itch caused by allergy.
As shown in fig. 4: the model group had significantly elevated guinea pig right ear eosinophil and mast cell numbers compared to the control group. Compared with the model group, the cell numbers related to the two inflammations and allergies of the dendrobe phenol group are obviously reduced, which suggests that the dendrobe phenol can obviously inhibit the inflammations and allergies.

Claims (6)

1. The application of dendrobinol as the only effective component in preparing medicines for treating allergic skin diseases.
2. Use of a composition comprising dendrobe as the sole active ingredient in the manufacture of a medicament for the treatment of allergic skin diseases.
3. The use according to any one of claims 1-2, wherein the allergic skin disease is: eczema, urticaria, contact dermatitis, atopic dermatitis, allergic purpura, and allergic drug eruptions.
4. The use according to claim 3, wherein the dendrobinol is formulated with the corresponding dosage forms of auxiliary materials into injections, pills, granules, solutions, suspensions, emulsions or microcapsules.
5. The use according to claim 3, wherein the composition comprises the following raw materials: dendrobe phenol, stearic acid, potassium carbonate, glycerol monostearate, triethanolamine and clove oil.
6. The use according to claim 5, wherein the ratio of dendrobinol, stearic acid, potassium carbonate, glycerol monostearate, triethanolamine, clove oil is 0.25g:0.55g:0.045g:0.5g:0.125g:0.015mL:0.035 And (3) mL.
CN202210294045.9A 2022-03-24 2022-03-24 Application of dendrobinol and composition thereof in preparation of medicines for treating allergic skin diseases Active CN114652706B (en)

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TW201249454A (en) * 2011-06-13 2012-12-16 Univ Tunghai Non-polysaccharide compound and usage thereof, and extraction method from Dendrobium genus plant
CN103494794B (en) * 2013-10-08 2015-08-19 上海中医药大学 The medical usage of Bibenzyl compound

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Inventor after: Wang Wei

Inventor after: Zhang Yang

Inventor after: Chen Shuangshuang

Inventor after: Wang Yiyuan

Inventor after: Li Yupeng

Inventor after: Hu Runfan

Inventor after: Chen Duyan

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